Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autosomal dominant polycystic kidney disease affect adults starting the 5th decade of life. It is caused by at least two different gene defects, one gene being located on the short arm of chromosome 16. It's more frequent at women and clinically, near renal cysts, appear others systemic manifestations as hepatic cysts, intracranial aneurysms, cardiac valvular lesions or diverticula. The diagnosis is set up on urography and ultrasonography and the treatment attempt to slow down the evolution to renal failure and to prevent the complications as infections, obstructions and hypertension, that may aggravate the prognosis. Lately there are discussions about a preventive treatment consisting in genetic counseling.
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PMID:[Polycystic kidney disease with autosomal dominant transmission]. 130 23

Autosomal dominant polycystic kidney disease (ADPKD) is one of the major causative diseases leading to renal failure and dialysis treatment. Although the genetic study on the disease has been progressed so far, the initial trigger for cyst formation and several factors enhancing the progression of ADPKD remain to be clarified. Using an animal model of ADPKD, induced by 2-amino-4,5-diphenylthiazole hydrochloride (DPT), we examined the early events in cytogenesis. Especially the role of tubular obstruction in the model in triggering off tubular dilatation was investigated by means of renal micropuncture and tubular microperfusion techniques. Light and electron microscopic studies demonstrated epithelial hyperplasia along collecting ducts after 2 weeks of DPT feeding. In addition, some collecting ducts revealed partial obstruction with hyperplastic cells. Cystic change became prominent over 8 weeks of the treatment. Then micropuncture and microperfusion experiments were performed to measure intratubular pressure in the rats fed DPT for 2-5 weeks (PKD rats) and pair-fed control Sprague-Dawley rats (control rats). Free flow pressure in proximal segments of PKD rats (21.5 +/- 1.0mmHg) was not significantly elevated, as compared with that in control rats (21.3 +/- 1.0mmHg). During the stepwise increments in proximal tubular flow rate, proximal tubular pressure in PKD rats significantly increased especially at higher flow rate, 41.0 +/- 3.6 mmHg in PKD rats and 19.4 +/- 3.1mmHg in control rats (P < 0.01) at 40nl/min. On the other hand, the transit time of loop of Henle was longer in PKD rats (38.9 +/- 2.4 sec) than in control rats (24.9 +/- 0.6 sec, P < 0.01). These results suggest that cyst formation in PKD rats could be preceded by the elevation of tubular resistance, which might be explained by the partial obstruction of collecting ducts. Moreover, these tubular obstruction in the distal segments might be the trigger for the cyst formation in this model.
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PMID:[Structure and function of the experimental polycystic kidney induced by diphenylthiazole with special reference to renal micropuncture study]. 148 5

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disorder leading to terminal renal failure. About 8% of the dialysis patients suffer from ADPKD, the gene frequency in the general population being about 1:1000. Many facts contribute to the hypothesis that arterial hypertension plays a major role in the pathophysiology of ADPKD. We observed a prevalence of 30% of hypertension in patients with ADPKD and normal serum-creatinine, and of 80% in patients with terminal renal failure. The time of onset of abnormalities of blood pressure regulation is of great interest, since an increase of blood pressure, even in the normotensive range, accelerates the rate of progression. To answer this question, we examined the time of onset of abnormalities in blood-pressure regulation in 23 probands and 23 control patients in a cross-sectional study. The results document abnormal circadian blood-pressure changes and higher blood pressures, although still within the normotensive range, in asymptomatic carriers of the ADPKD-trait, even before and more definitely after onset of puberty. Even at an age when circadian blood pressure is not significantly different, there is an increased LVM as evidence of target organ damage. The findings suggest that (intermittent) increases in blood pressure and blood-pressure-dependent target organ damage precede overt hypertension and renal failure by years or decades.
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PMID:[Ambulatory 24-hour blood pressure monitoring of children and young adults with autosome dominant polycystic kidney degeneration]. 151 6

Polycystic kidney disease is a bilateral disorder that affects approximately 200,000-400,000 persons in the United States. The most common form of the disease is inherited as an autosomal dominant trait (ADPKD). It typically causes renal insufficiency by the fifth or sixth decade of life. The disease is characterized by the progressive enlargement of a portion of renal tubule segments (proximal, distal, loop of Henle, collecting duct). The tubules enlarge from a normal diameter of 40 microns to several centimeters in diameter, causing marked gross and microscopic anatomic distortion. The cause of the cystic change in the tubules is unknown, but current possibilities include obstruction of tubule fluid flow by hyperplastic tubule cells, increased compliance of the tubule basement membranes, and/or increased radial growth of cells in specific portions of the renal tubule. Several studies show that the epithelia of the cysts continue to transport Na+, K+, Cl-, H+, and organic cations and anions in a qualitative fashion similar to that of the tubule segment from which they were derived. ADPKD, then, is a disease in which some gigantic renal tubules, over a period of several decades, impair the function of nonaffected nephrons and thereby lead to renal failure.
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PMID:Polycystic kidney disease: a predominance of giant nephrons. 633 12

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease which frequently results in renal failure. The major ADPKD gene, polycystic kidney disease 1 (PKD1), has recently been identified. In an attempt to understand better the aetiology of this disorder we have searched for mutations in the PKD1 gene. Analysis of three regions in the 3' part of the gene has revealed two mutations that occur by a novel mechanism. Both mutations are deletions (of 18 or 20 bp) within the same 75 bp intron and although these deletions do not disrupt the splice donor or acceptor sites at the boundary of the intron, they nevertheless result in aberrant splicing. Two different transcripts are produced in each case; one includes the deleted intron while the other has a 66 bp deletion due to activation of a cryptic 5' splice site. No normal product is generated from the deleted gene. Aberrant splicing probably occurs because the deleted intron is too small for spliceosome assembly using the authentic splice sites; this mechanism has previously only been described from in vitro studies of vertebrate genes. A 9 bp direct repeat has been identified within the intron, which probably facilitated deletion by promoting misalignment of sequence. The possible phenotypic implications of producing more than one aberrant PKD1 transcript in these cases are discussed.
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PMID:Splicing mutations of the polycystic kidney disease 1 (PKD1) gene induced by intronic deletion. 763 5

The Han: SPRD Pkd rat mutant is an autosomal dominant rat model with incomplete penetration of polycystic renal transformation. Progressive renal failure occurs in heterozygous male animals. The mechanisms of progression have not been elucidated. To identify some pathogenetic factors involved we subjected male SPRD Pkd rats (and their non-affected littermates as controls) to uninephrectomy (UNX), castration or enalapril treatment. To assess progression S-urea at age 150 days was chosen as endpoint. (i) In uninephrectomized male Han: SPRD Pkd (n = 12 animals per group) S-urea at age 150 days was consistently above 300 mg/dl, while it was 245 mg/dl (191-290) in control Han: SPRD Pkd. (ii) In castrated male Han: SPRD median S urea at 150 days was 100 mg/dl (69-211) compared to sham-operated male Han: SPRD controls (245; 191-290). Castration did not, however, prevent accelerated progression after uninephrectomy. (iii) Enalapril (50 mg/l) in the drinking fluid did not significantly lower median systolic blood pressure (by plethysmography) in animals on 0.2% sodium diet (at 185 days 160 mmHg; 140-170 versus 170; 140-195 in non-enalapril controls), although circulating ACE was significantly inhibited (17 U; 11-33 versus 89; 52-108 in controls). S-urea at age 185 days was not significantly different in the 2 groups. In conclusion, the Han: SPRD Pkd model differs from human ADPKD to some extent. Uninephrectomy accelerates renal failure in the rat, but not in humans. On the other hand, in contrast to human ADPKD the renin system is suppressed in the rat model and ACE inhibition does not affect the course of renal failure.
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PMID:Progression of renal failure in the Han: SPRD polycystic kidney rat. 770 56

Polycystic kidney disease is a rather common genetic disorder, with an estimated amount of 8 to 10% of patients in the dialysis population. Meanwhile the defective gene of autosomal dominant polycystic kidney disease [ADPKD], another common terminus for this disorder, has been localized on the short arm of chromosome 16. The genetic disorder is not strictly localized on the kidney, whereas other organ systems like cardiac valves, brain arteries, liver, colon, etc. may be involved in the disease process. Hypertension is an early and common feature of the disease and its probably an important factor for progression of renal failure in ADPKD. Not all carriers of the ADPKD-trait progress to endstage renal failure, about 50% at the age of 50 years. Patients with ADPKD have a good prognosis in renal replacement therapy programs such as dialysis or renal transplantation.
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PMID:[Cystic kidneys (autosomal dominant polycystic kidney disease)]. 778 92

Autosomal dominant polycystic kidney disease (ADPKD) characteristically leads to end-stage renal failure in the fifth or sixth decade of life, which in the absence of therapeutic measures will lead to premature death. To determine excess mortality relative to the general population and chromosome 16-linked ADPKD patients, we studied 348 individuals who belonged to five large ADPKD families and who had at least a 50% probability of carrying the gene; the study data derive from a time span of approximately one century. Assessment of the diagnosis of ADPKD in the present generation was based on the characteristic roentgenographic appearance of polycystic kidneys and was confirmed by DNA analysis with flanking polymorphic markers around the polycystic gene. In the previous generation, we used Mendelian reasoning after pedigree analysis to identify persons with a 50% or 100% probability of carrying the polycystic gene. During the study period (1889 to 1992), 83 deaths occurred in 10,279 person-years. Mortality was increased 1.6-fold (95% confidence interval, 1.3 to 2.0) relative to the general population and was independent of the gender of the affected family member as well as the gender of the transmitting parent. The increased mortality was strongest in the 50 to 59 year age group (relative mortality, 3.2; 95% confidence interval, 2.0 to 4.8), but decreased after the 1970s, probably as a result of improvements in supportive care and, eventually, renal replacement therapy. In conclusion, the total life-span in ADPKD patients is improving, but remains low in comparison to the general population, and the gender of the transmitting parent or of the affected individual does not influence relative mortality.
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PMID:A century of mortality in five large families with polycystic kidney disease. 787 13

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently results in renal failure due to progressive cyst development. The major locus, PKD1, maps to 16p13.3. We identified a chromosome translocation associated with ADPKD that disrupts a gene (PBP) encoding a 14 kb transcript in the PKD1 candidate region. Further mutations of the PBP gene were found in PKD1 patients, two deletions (one a de novo event) and a splicing defect, confirming that PBP is the PKD1 gene. This gene is located adjacent to the TSC2 locus in a genomic region that is reiterated more proximally on 16p. The duplicate area encodes three transcripts substantially homologous to the PKD1 transcript. Partial sequence analysis of the PKD1 transcript shows that it encodes a novel protein whose function is at present unknown.
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PMID:The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16. The European Polycystic Kidney Disease Consortium. 806 19

Autosomal dominant polycystic kidney disease (ADPKD) is a disorder of adult onset manifested by bilaterally enlarged cystic kidneys frequently associated with progressive renal failure. The mutated gene (PKD1) responsible for 85 to 95% of cases has been localized to a small segment on the distal tip of the short arm of chromosome 16. A clinical spectrum of heritable connective tissue disorders that remain unclassifiable under the present nosology but that contain elements of the Marfan's syndrome have previously been described. The genetic localization and molecular basis of such overlap connective tissue disorders (OCTD) have not been elucidated. In this report, a kindred in which ADPKD and OCTD appear to cosegregate is described. The connective tissue phenotype in this family includes aortic root dilation, aortic and vertebral artery aneurysms with dissection, and aortic valve incompetence, as well as pectus abnormalities, pes planus, joint laxity, arachnodactyly, scoliosis, dolichostenomelia, and high arched palate. ADPKD was manifest primarily as bilateral renal cysts with or without renal failure. The DNA of all living family members was studied with markers recognizing polymorphic loci flanking the PKD1 region (3'HVR and O90a), as well as markers from the loci of chromosomes 15 and 5, associated with fibrillin genes FBN1 and FBN2, respectively. In this kindred of 20 family members traced through five generations, cosegregation of ADPKD and the OCTD phenotype was observed in 12 of 12 meioses and 3 of 3 phase known. Both markers for PKD1 were tightly linked to both ADPKD and OCTD, whereas there was no evidence for linkage with either fibrillin locus. In this family, the ADPKD and OCTD mutations are genetically linked. The presence of OCTD with ADPKD identifies a group of patients at significantly greater risk for sudden death from aortic root and other vascular aneurysmal dissection and rupture.
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PMID:A kindred exhibiting cosegregation of an overlap connective tissue disorder and the chromosome 16 linked form of autosomal dominant polycystic kidney disease. 813 Mar 64


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